The present invention relates to a method of, and apparatus for, analyzing particles dispersed in a fluid, especially a liquid containing a blood sample.
In its more particular aspects, the present invention specifically relates to a method of, and an apparatus for, analyzing particles dispersed in a fluid and which apparatus comprises first storage means as well as a first computing section and a second computing section for determining separation threshold values which are utilized for the particle analysis in the fluid, particularly the liquid containing the blood sample. Such separation threshold values are determined on the basis of measured values of a predetermined particle parameter and the number of particles which are associated with the measured values and are dispersed in the particle containing fluid. The predetermined particle parameter, for example, may constitute the size or volume of the analyzed particles such as, for example, blood cells in a blood containing liquid sample.
The measured values are arranged in the form of individual histograms which are related to individual samples of the particle containing fluid. Each one of the individual histograms contains at least two particle population maxima and at least two particle population minima. At least one of the at least two particle population minima is determined using conventional adaptive techniques.
Each individual sample of the particle containing fluid or fluid mixture, especially a liquid containing a blood sample, contains particles of different species or classes which differ with respect to, for example, the particle size or volume. Such different species or classes of particles are present in different samples of the particle containing fluid in corresponding different particle distributions or particle distribution densities. Such different particle distributions or particle distribution densities are expressed by the different particle population maxima in the aforementioned individual histograms. Consequently, during the particle analysis of a particle containing fluid or fluid mixture, especially a liquid containing a blood sample, there is required a differentiation between the different particle distributions or particle distribution densities of the various particle species or particle populations. This differentiation is effected by analyzing the individual histograms utilizing so-called separation threshold values. Such separation threshold values can also be utilized to differentiate or discriminate between overlapping particle distributions or particle distribution densities of the various species or populations. In any case, the separation threshold values are set at predetermined particle population minima such as to permit substantially error-free evaluation of the individual histograms in terms of the different particle populations.
Multifarious criteria exist for setting the aforementioned separation threshold values in the individual histograms or particle distributions which are obtained as the result of the measurement of the aforementioned measured values of the predetermined particle parameter and the number of particles which are associated with such measured values. In accordance with corresponding criteria there can be differentiated in principle between fixedly set separation threshold values and adaptive separation threshold values which "follow" the particle populations in the individual histograms. The method and apparatus according to the present invention can be used with both types of separation threshold values. Most preferred, however, is the utilization of the present invention in conjunction with adaptive separation threshold values.
In an apparatus such as known, for example, from European Patent Publication No. 0,012,418, published June 25, 1980, cognate with the aforementioned U.S. Pat. No. 4,309,757, granted Jan. 5, 1982, there can be analyzed, for example, a correspondingly prepared liquid containing a blood sample for erythrocytes. The apparatus carries out appropriate operations or steps and contains appropriate means for automatically, i.e. adaptively finding the separation threshold value associated with a particle population minimum in the histogram which is obtained as a result of the investigation of the liquid containing the blood sample which contains a bimodal distribution of the particle size. Such adaptively determined separation threshold value which is associated with a related particle population minimum in the individual histogram, permits discriminating or differentiating between overlapping size or volume distributions of the particles contained in the particle containing fluid sample.
Multimodal distributions containing overlapping particle populations show markedly differently distinct or resolved particle population maxima and particle population minima. Practically, the particle population minima exclusively serve as a criterium for the separation or resolution between two overlapping particle populations. Generally, the particle population maxima are not used as separation or resolution or differentiation criteria. Frequently, however, the desired particle population minima are insufficiently distinctly formed or resolved and, as a consequence, the detection or location of a suitable separation threshold value already fails solely for the reason of such insufficient resolution.
Thus, for example, with liquids containing blood samples having relatively small lymphocyte concentrations, there exists the problem that the desired particle population minima frequently are insufficiently distinct or resolved whereby the detection or setting of a useful separation threshold value is not ensured.